ADP-ribosylation factor-like 6 interacting protein 5 (ARL6IP5)

ADP-ribosylation factor-like 6 interacting protein 5 (ARL6IP5) is a multifunctional membrane-associated protein of the PRA1 family containing four transmembrane domains. It is mainly located in the endoplasmic reticulum, where it participates in shaping ER morphology and regulating ER-phagy. ARL6IP5 is involved in diverse biological processes including intracellular protein transport, regulation of cell apoptosis (especially during differentiation and under stress via MAPK and ER stress pathways), modulation of glutamate transporter EAAC1 (affecting neuronal function), and DNA damage repair (interacting with XRCC1 and PARP1). Its roles are context-dependent—acting as both a tumor suppressor and oncogene in different cancers, influencing chemotherapy resistance, and impacting bone remodeling and neuroprotection. ARL6IP5 is being actively studied for its relevance in cancer, neurodegenerative diseases, and skeletal disorders, and its expression is associated with patient prognosis in several cancer types[1][2][3][4][5].

Other names

JWAADDICSINGTRAP3-18PRAF3HP22HSPC127DERP11JMXYip6bJM5PRA1 family protein 3

ARL6IP5 promotes apoptosis by suppressing DNA repair proteins (e.g., XRCC1, PARP1), especially under chemotherapy. It also modulates MAPK signaling, affecting cellular responses to stress and apoptosis. Furthermore, it regulates glutamate uptake, impacting neuronal excitotoxicity, and can induce ER stress, leading to cell death or altered differentiation.